Heme Lymph Exam 1 Flashcards
(324 cards)
1
Q
where does hematopoiesis occur
A
early embryo - yolk sac mesoderm
second trimester - primarily liver and some spleen
third trimester - bone marrow (primary skeletal element changes over time)
2
Q
composition of blood
A
RBC - 35-50%
buffy coat (leukocytes and platelets) - 1% or less
plasma - 49-57%
3
Q
hematocrit
A
volume of packed erythrocytes in blood
men: 39-50%
women: 35-45%
-low hematocrit means reduced circulating RBCs or significant blood loss
4
Q
plasma
A
composed of proteins, inorganic salts, organic molecules
5
Q
serum
A
plasma minus the clotting factors
gets squeezed out of blood clots
6
Q
formed elements of the blood
A
erythrocytes
leukocytes
platelets
7
Q
what parts of blood can move into peripheral tissues
A
leukocytes and plasma
8
Q
staining patterns
A
basophilia - deep blue (RNA/DNA)
azurophilia - purple (lysosomes)
eosinophilic - pink (hemoglobin/granules)
neutrophilic - light pink/lilac (neutrophilic granules)
9
Q
erythrocytes
A
anucleated biconcave disks
33% hemoglobin
7.5 um in diameter
macrocytes >9 um
microcytes <6 um
deformability due to membrane peripheral proteins on hemoglobin (HgA)
10
Q
sickle cell disease
A
HbS - point mutation in beta globin chain replacing glutamic acid with valine
polymerizes when deoxygenated into rigid aggregate
11
Q
reticulocytes
A
immature red blood cells
basophilic staining ribosomes , can synthesize hemoglobin
become mature in 1-2 days using ATP dependent cytoplasmic enzymes to degrade organelles
12
Q
how long do RBCs stay in circulation
A
120 days
13
Q
how do RBCs get energy
A
from glucose
14
Q
how are senescent RBCs removed
A
by macrophages in spleen and bone marrow
15
Q
hemoglobin bound to oxygen
A
oxyhemoglobin
16
Q
hemoglobin bound to carbon dioxide
A
carbaminohemoglobin
17
Q
hemoglobin bound to carbon monoxide
A
carboxyhemoglobin
18
Q
leukocytes
A
migrate into tissues from blood circulation by diapedesis
host defense against invading microbes and tumors
granulocytes and agranulocytes
usually 6,000 - 10,000
19
Q
granulocytes
A
neutrophils, eosinophils, basophils
multilobed nucleus with specific and azurophilic granules
20
Q
agranulocytes
A
lymphocytes, monocytes
only have azurophilic granules
nucleus not lobulated
21
Q
neutrophils
A
polymorphonuclear lymphocytes (PMNL)
60-70% WBC count
2-5 nuclear segments connected by tapering chromatin strands
first to arrive at site of infection
22
Q
phagocytosis
A
neutrophils and monocytes/macrophages
pseudopodia surround particles and fuse to form phagosome
specific granules fuse and dump contents into phagosome (proton pump lowers pH)
azurophilic granules fuse and dump contents
23
Q
neutrophil cytoplasmic granules functions
A
azurophilic primary granules - kill/degrade microorganisms
specific secondary granules - secretion of various ECM degrading enxymes, deliver bactericidal proteins to phagolysosome
24
Q
neutrophil specific granules
A
ellipsoid shape
enzymes - type IV collagenase, gelatinase, phospholipase
complement activators
antimicrobial peptides
25
neutrophilic defect
often genetic
decrease venule wall adhesion
26
eosinophils
2-4% WBC count
bilobed nucleus
eosinophilic specific granules and few to no azurophilic granules
helminth infections and allergic reactions
remove antigen antibody complex from interstitial fluid
in CT of intestinal lining and sites of chronic inflammation
27
eosinophilic specific granules
elongated oval shaped bodies
crystalloid body - crystalline core called the internum and surrounding layer of granule called externum
proteins - major basic protein (MBP), eosinophil cation protein (ECP), eosinophil peroxidase (EPO), eosinophil derived neurotoxin (EDN)
histamine, arylsulfatase, collagenase, cathepsins
28
basophils
less than 1% WBC count
multilobed nucleus
metachromatic specific granules that are irregular size and shape
few to no azurophilic granules
secrete granular components in response to certain antigens and allergens (similar to mast cell)
29
basophilic specific granules
eosinophilic chemotaxic factor
heparin and other sulfated GAGs
histamine and other inflammation mediators
peroxidase
30
anaphylaxis
second exposure to allergen
basophils and mast cells degranulate
vasodilation and sudden drop in blood pressure
31
type 1 hypersensitivity
production of IgE antibodies
bind receptors on mast cells and basophils
subsequent exposure - allergen combines receptor bound IgE molecule
bronchial asthma, cutaneous hives, rhinitis, conjunctivitis
32
lymphocytes
20-30% WBC count
distinguished into functional subpopulations by surface marker expression
B lymphocytes, helper (CD4) and cytotoxic (CD8) T cells, NK cells
round nucleus, scanty cytoplasm, many free polyribosomes
33
B lymphocyte
10-20% total lymphocytes
mediate humoral immunity and production of anitbodies
formed in bone marrow
have antibody molecule receptor for antigen on membrane
-plasma cell is terminally differentiated which secretes antibody in different immunoglobulin classes
34
plasma cells
cytoplasm basophilic
clear are near nucleus where golgi body is
nucleus is round and eccentrically placed
chromatin pattern is cartwheel
35
T lymphocytes
70-80% total blood lymphocytes
precursors formed in bone marrow, mature in thymus
long life span
cell mediated immunity
36
NK cells
develop from same precursor as b and t cells
programmed to kill certain virus infected and tumor cells
secrete antiviral agents
larger than b and t cells
37
lymphomas
neoplastic proliferation of lymphocytes
failure of cells to undergo apoptosis
slow growing but spread easily
38
monocytes
3-8% of total blood WBC
immune defense and tissue repair
nucleus is oval/horse shoe/ kidney bean shaped and usually eccentric
chromatic less condensed and more fibrillar arrangement
many fine azurophilic granules
differentiate into macrophage
interact with lymphocytes and role in recognition/interaction of t cells and antigen
39
platelets
thrombocytes
very small, non nucleated, membrane bound cell fragments
from cytoplasmic processes of megakaryocytes
promote clotting
hyalomere peripherally
granulomere centrally
40
platelet functions
primary aggregation - platelet plug when platelet glycocalyx adheres to vessel
secondary aggregation - more platelets aggregate and ADP released
blood coagulation - fibrin polymer forms network to trap RBCs and platelets
clot retraction - platelet derived actin and myosin cause contraction
clot removal - clot dissolved by proteolytic enzyme
41
what is the best CBC sample
venipuncture (venous blood draw with 22 gauge or larger needle)
placed in tube with anticoagulant and mixed
42
automated counting of formed elements can be done by
electrical impedance
flow cytometry (white blood cells)
43
indication for bone marrow examination
unexplained change in blood cell counts
44
sensitivity
percentage of individuals with disease that get a positive result
45
specificity
percentage of individuals without disease that get a negative result
46
hematocrit
percent of blood taken up by red blood cells
47
hemoglobin
amount of hemoglobin in a volume of blood
48
mean corpuscular volume
average red blood cell volume (ssize)
49
reticulocytes
immature rbcs w/o a nucleus (measure of RBC production)
50
red cell distribution width
variance of the width of RBCs
51
mean corpuscular hemoglobin
average mass of hemoglobin per RBC
52
mean corpuscular hemoglobin concentration
average concentration of hemogllobin in a given volume of red cells (how much hemoglobin is inside 1 red blood cell)
53
how is plasma separated
by salting out using ammonium sulfate
54
albumin
most abundant plasma protein
affects osmolarity and produces osmotic effects like sterling forces (pressure causes water to leave capillaries at arteriol, lower pressure in venule allows it to reenter)
produced by liver (signal peptide removed as it moves through ER then hexapeptide cleaved off amino terminal)
*low albumin leads to fluid retention (liver disease/kwashiorkor)
55
functions of albumin
maintain blood volume and fluid distribution
binds materials for circulation (hydrophobic and ions)
buffer amount of dissolved materials, bound materials act as reservoir
56
fatty acids and albumin
transport from lipolysis in adipocytes to muscle/heart/liver
used as fuel or lipid synthesis
multiple binding sites on albumin
cannot cross BBB
57
bilirubin and albumin
bound material relatively safe and not filtered by kidney (unbound is toxic)
produced constantly and albumin transports to liver safely to be detoxified
removal of unbound lets more bound material leave albumin
58
analbuminemia
lack serum albumin
other proteins elevated
various symptoms noted
59
familial dysalbuminemic hyperthyroxinemia
mutation changes affinity for thyroid hormones
alters free thyroid hormone levels
usually doesnt require therapy
60
globulins
alpha 1 - produced in liver (alpha 1 antitrypsin)
alpha 2 - produced in liver (haptoglobin, ceruloplasmin, alpha 2 macroglobulins)
beta - produced in liver (transferrin, c reactive protein, hemopexin, complement C1q)
gamma - synthesized in plasma cells and b cells in lymphoid tissue (increase in chronic infection, autoimmune disease, leukemia)
61
alpha 1 antitrypsin
alpha 1 antiprotease
main serine protease inhibitor of plasma
protect against neutrophil elastase
inactivated by myeloperoxidase (necessary at inflammation sites)
62
alpha 1 antitrypsin deficiency
mild - emphysema in 4th decade
severe - protein trapped in liver endoplasmic reticulum, can lead to liver disease in children
63
haptoglobin
binds free hemoglobin (unbound free hemoglobin degrades NO causing oxidative stress, hemoglobin binds CD163 on monocytes and hemoglobin degraded)
concentration rises in inflammatory conditions
concentration decreases in hemolytic anemias
genetics - Hp1 better direct antioxidant (has multiple structures), Hp2 one structure, Hp1/Hp2 multiple structures
64
ceruloplasmin
binds copper atoms (necessary to enzymes but can be toxic)
storage reservoir and transport
changes oxidation state of iron for protein binding
65
alpha 2 macroglobulin
binds proteases and changes conformation so other molecules can bind
can attach to receptors on liver macrophages
endocytosis clears proteases and cytokines to slow down stimulation of immune cells
66
transferrin
major protein for iron binding and transport (binds Fe3+)
made in many tissues but mostly liver
has 2 binding sites
taken into cells and releases iron into endosomes
67
c reactive protein
reacts with C polysaccharide capsule of pneumococci
stimulates complement activity and macrophages
rises in inflammatory conditions
biomarker for coronary heart disease
68
hemopexin
bind to heme formed from breakdown of Hb and hemoproteins
low levels in hemolytic disorders
69
complement proteins
bind immunoglobulins on cells
form complex that create hole in cell membrane
70
complement C1q
first complement factor to bind antibody
binds IgG or IgM and triggers classical complement path
high levels in chronic infections
71
immunoglobulins
made by B cells and plasma cells
role in defense mechanisms of body
various classes, undergo class switching
72
fibrinogen
clotting factor 1
largest contributor to blood viscosity
amino terminal is very negative bc glutamic acid (contributes to sulibility in plasma)
73
retinol binding protein
binds retinol (form of vitamin A)
transport from liver to peripheral tissues
bound to tranthyretin
prevents filtration by kidney
74
transthyretin
binds RBP and thyroxin
major binding protein of thyroxin in CSF
made in liver and choroid plexus
2 RBPs bind 1 transthyretin
transthyretin monomers bad and cause amyloidosis disorders
75
acute phase proteins in inflammatory conditions
increase (CRP, ceruloplasmin, alpha 1 antitrypsin, alpha 2 macroglobulins)
decrease (albumin, transthyretin, retinol binding protein, tranferrin)
76
platelet binding
endothelial damage exposes phospholipids, collagen, and proteins (like vWF)
glycoprotein 1a binds collagen and the platelet changes shape to gain interation
glycoprotein 1a binds vWF and exposes glycoprotein 2b and 3a that bind vWF and fibrinogen
77
platelet activation
platelet binding causes the release of ADP which exposes more GP 2b and 3a, causing platelets to swell
increased contact and adherence of platelet to one another
fibrinogen released
78
intrinsic pathway
factor 12 changes to 12a
factor 11 changes to 11a using thrombin
factor 9 changes to 9a using 11a or 7a, phospholipids, and collagen *this is key
factor 8 changes to 8a using thrombin
factor 10 changes to 10a using 8a, 9a, phospholipids, and collagen
79
extrinsic pathway
trauma
calcium, phospholipids, and tissue factor (3) released
factor 7 to 7a autocatalytically
factor 10 to 10a using ca and phospholipids
80
common path
factor 10a complexes with 5a and 2 (prothrombin) to change prothrombin to thrombin (requires ca and phospholipids)
cleaves fibrinogen to fibrin
81
protein c
processing: de novo synthesis in liver and glycosylation, carbocylation and hydroxylation, dipeptide release, activation peptide release and activation
complexes with protein s
inhibits factor 5 and 8
82
fibrin cross linking
done by factor 13
transglutaminase activity links glutamine to lysine
83
regulating coagulation
thrombin binds thrombomodulin on endothelial surface
this activates protein c which complements with protein s to remove factor 5a and 8a
84
natural anticoagulants
heparin - binds and activates antithrombin 3
antithrombin 3 inactivates thrombin, blocks fibrin formation and factor activation
antithrombin also binds 8a, 9a, 10a, 11a to decrease availability
85
clot dissolution
major enzyme is plasmin (made as inactive plasminogen, high affinity for fibrin)
plasminogen activator from endothelial cells is highly active activator
86
hemophilia A
x linked gene for factor 8
mild, moderate, or severe depending on specific mutation
lack factor 8 which is normally part of activation of factor 10 at start of common path
decreases fibrin production
87
hemophilia b
defect in factor 9 gene on x chromosome
serine protease that activates factor 10 after factor 8a binds
88
von willebrand disease
autosomal
usually only problem with patients who have surgery or severe trauma
affects platelet plug formation and cascade (decreased factor levels without vWF)
89
red bone marrow
produces blood
all bone marrow is this type in newborns
90
yellow bone marrow
filled with adipocytes
most bone marrow eventually becomes this
91
sinusoidal endothelium of bone marrow
where newly formed erythrocytes, leukocytes, and platelets enter circulation
- leukocytes cross wall by their own motility
- erythrocytes enter circulation pushed by pressure gradient
- megakaryocytes form thin processes that pass through apertures and liberate platelets at their tips
92
hemopoiesis lineage summary
stem cells (pluripotent or multipotent, self renewing)
progenitor cells (colony forming units, restricted potential)
precursor cells/blasts (high mitotic activity, series of acquiring mature characteristics)
cytes (mature cells)
93
erythropoiesis
proerythroblast (basophilic cytoplasm with ribosomes making hemoglobin)
basophilic erythroblast (basophilic cytoplasm still making globin)
polychromatophilic erythroblast (splotchy cytoplasm with basophilic ribosomes and eosinophilic hemoglobin)
orthochromatophilic erythroblast (uniformly eosinophilic with cytoplasm filled with hemoglobin)
nucleus ejected
reticulocyte (enter circulation, some ribosomes still making hemoglobin)
erythrocyte
94
thrombopoiesis
megakaryoblast (basophilic cytoplasm, several nucleoli)
promegakaryocyte (endomitosis, repeated DNA without dividing)
megakaryocyte (very large, polyploid nuclei that are irregularly lobulated with coarse chromatin)
thrombocytes (have mitochondria, no nucleus, some DNA, mRNA from parents for making proteins)
95
granulopoiesis
myeloblast (no cytoplasmic granules)
promyelocyte (azurophilic granules secreted, similar in all 3 types)
myelocyte (production of specific granules gives the types distinct characteristics)
metamyelocyte (abundant granules, golgi reduced, nucleus changes shape)
96
neutrophil compartments
granulopoietic compartment in marrow
storage in marrow waiting for release
circulating cells
marginating cells accumulating along endothelial surface (may or may not emigrate into tissue)
inflammed tissue (cells migrate here then die by apoptosis)
97
monocytopoiesis
monoblast
promonocyte
monocyte
macrophage (after leaving vasculature into tissues)
98
lymphopoiesis
lymphoblast
NK cell/T cell/B cell
dense spherical nucleus surrounded by rim of cytoplasm
99
thrombosis
clot that develops in flowing blood
has lines of zahn
100
partial thromboplastin time
intrinsic and common path
12, 11, 9, 8
10, 5, 2, fibrinogen
101
prothrombin time
extrinsic and common path
7
10, 5, 2, fibrinogen
102
thrombin time
fibrinogen to fibrin in common path only
103
d dimer
elevated with thrombosis bc clot formation and lysis
fibrin degradation products are measures
104
thrombophilia
increased risk of thrombosis
inherited (factor 5 mutation, protein C deficiency) and acquired
105
factor 5 Leiden mutation
autosomal dominant
homozygotes affected more than heterozygotes
resistance to protein C activity which alters the balance between pro and antithrombic effects in favor of thrombosis
indications - recurrent/early/unprovoked DVT/VTE, recurrent pregnancy loss, family history
testing - APC resistance, genetic testing for mutation, Protein S and C deficiency, prothrombin mutation
tx- anticoagulation, exercise, stop smoking, lose weigh, manage meds
106
acquired hypercoagulability
heparin induced thrombocytopenia
antiphospholipid antibody syndrome
smoking, hyperestrogenic states, oral contraceptives, sickle cell anemia
107
heparin induced thrombocytopenia
administration of unfractionated heparin
induce appearance of antibodies that recognize complexes of heparin and platelet factor 4
binding of antibody to platelets causes activation, aggregation, consumption causing prothrombic state and low platelet counts
108
antiphospholipid antibody syndrome
binding of antibodies to epitomes on membrane proteins that are induced by phospholipids
antibody targets are plasma proteins that associate with surfaces of endothelial cells and trophoblasts and may bind other proteins inducing hypercoagulable state
109
vessel wall abnormalitites
increased fragility of vessels causing bleeding
infections, immune reactions, amyloidosis, scurvy, ehler danlos
110
thrombocytopenia
reduced platelet numbers
spontaneous bleeding can occur
111
chronic immune thrombocytopenia purpura
autoantibodies (IgG) to platelets (factor 2b,3a, or 9) causing destruction
autoantibodies can bind megakaryocytes and decrease platelet production
primary or secondary
giant platelets seen in blood, increased number megakaryocytes
tx - glucocorticoids, immune modulating agents, splenectomy
may need antibiotics for life
112
acute immune thrombocytopenia purpura
in children, secondary to antibodies to platelets
self limiting, treated with glucocorticoids if severe
113
thrombotic thrombocytopenia purpura
most often acquired, can be familial
deficient metalloprotinease leads to large vWF multimers
widespread thrombi with consumption of platelets and thrombocytopenia
thrombocytopenia (bruising), hemolytic anemia (jaundice), end organ damage may occur
decreased platelets, fragmented RBCs
tx - daily plasma exchange, splenectomy
114
bernard soulier
defective platelet functioning
impaired binding of platelet to vWF and increased bleeding
variable, often severe, bleeding tendency
115
glanzmann syndromes
problem with receptor involved with fibrinogen bridging of platelets
bleeding often severe
116
disseminated intravascular coagulation
systemic activation of coagulation leads to consumption of factors and platelets
produce bleeding, vascular occlusions, hypoxemia
triggers - sepsis, major trauma, cancer, obstetric complications
117
factor XI deficiency
PT normal or slightly prolonged
PTT prolonged
affects intrinsic pathway
118
factor VII deficiency
PT prolonged
PTT normal
affects extrinsic pathway
119
factor X deficiency
PT prolonged
PTT prolonged
affects common pathway
120
vWF deficiency
PT normal or slightly prolonged
PTT prolonged
stabilizes factor VIII in intrinsic path
121
Disseminated intravascular coagulopathy
PT prolonged
PTT prolonged
consumes clotting factors
122
vitamin K deficiency
PT prolonged
PTT prolonged
needed for factors II, VII, IX, X
extrinsic path affected first
123
antiplatelet drugs
aspirin, clopidogrel, ticagrelor, prasugrel, cangrelor, eptifibatide, tirofiban, dipyridamole, cilostazol, vorapaxar
124
arterial thrombi
atheroscleosis
plaque rupture causing clot
MI - clot in coronary artery
stroke - clot in brain artery
antiplatelet
125
venous thrombi
vein injury, immobility, inherited disorders causing clot
DVT - clot in vein
PE - DVT clot break off and travel to pulmonary artery
anticoagulant
126
antiplatelet therapy
secondary prevention of coronary artery disease (MI) and stroke
component of management of acute coronary syndrome
component of management of acute ischemic stroke (TIA)
127
what is secreted by platelets to induce platelet aggregation
thromboxane A2 (TXA2)
ADP
128
what are the 2 main ADP receptors
P2Y12 and P2Y1
129
what does TXA2 bind/do
binds thromboxane A2 receptor and activates g proteins to activate GPIIb/IIIa receptors
130
what happens when GP IIb/IIIa receptors are activated
change is made on the membrane so fibrinogen can bind and cross link platelets to make plug
131
what does thrombin do
convert fibrinogen to fibrin
activate platelets via PAR1 and PAR4 to release ADP and TXA2
132
antiplatelet meds targets
TXA2 synthesis via irreversible cox inhibition (aspirin)
block P2Y12 receptor preventing activation of GP IIb/IIIa (clopidogrel, ticagrelor, prasugrel)
block GP IIb/IIIa receptors to inhibit fibrinogen binding (eptifibatide, tirofiban)
antagonize PAR 1 receptor inhibiting thrombin induced aggregation (vorpaxar)
inhibit phosphodiesterase which breaks down cAMP to increase cAMP which is an antiaggregant (dipyridamole, cilostazol)
133
aspirin
for acute coronary syndrome, acute ischemic stroke, secondary for atherosclerotic CVD, off label prophylaxis for total hip/knee arthroplasty
adverse effects - GI upset, tinnitis, hypersensitivity reaction, bleeding
134
clopidogrel
prodrug - requires conversion by CYP2C19
for acute coronary syndrome (dual antiplatelet regimen with aspirin), acute ischemic stroke, secondary to reduce MI and stroke in pts with recent MI/stroke/peripheral atherosclerotic disease
adverse effects - thrombotic thrombocytopenic purpura, hypersensitivity
135
prasugrel
for acute coronary syndrome (pts managed with PCI)
CONTRAINDICATED history TIA/CVA
higher risk of bleeding
aderse effects - TTP, hypersensitivity
prodrug but uses different CYP enzyme
136
ticagrelor
for acute coronary syndrome (dual regimen with <100 mg aspirin), acute ischemic stroke, secondary prevnetion for MI/stroke in pts with ACS or hx MI, primary prevention for MI and stroke in pts with coronary artery disease at high risk
bind reversibly to area distinct from ADP site
BBW for bleeding risk
adverse effects - dyspneae, sleep apnea, bradyarrhythmias and ventricular pause, TTP
137
cangrelor
IV bolus
alternative to P2Y12 inhibitor if in cardiogenic shock or cannot take PO
138
drug induced thrombotic thrombocytopenia purpura
thrombotic microangiopathy caused by small vessel platelet thrombi, cause thrombocytopenia from platelet consumption, cause hemolytic anemia as RBCs fragmented by turbulent circulation
139
eptifibatide and tirofiban
IV bolus then continuous infusion
for acute coronary syndrome (pts undergoing primary PCI)
CONTRAINDICATIONS - active bleeding in last 30 days, history of stroke within 30 days, severe HTN
140
dipyridamole
in tablet combined with aspirin
for secondary prevention of ischemic stroke
adverse effects - headache, hypotension, GI
141
cilostazol
for intermittent claudication in peripheral artery disease
CONTRAINDICATED in heart failure of any kind
adverse effects - headache, diarrhea, dizziness, palpitations
interations with CYP inhibitors
142
vorapaxar
for histiry of MI or established peripheral arterial disease
long half life
BBW - bleeding risk, dont use in pts with history of stroke or intracranial hemorrhage
143
acute STEMI/NSTEMI
dual antiplatelet therapy with aspirin and P2Y12 inhibitor
144
choice of P2Y12 inhibitor
more potent for acute coronary syndrome who require PCI (ticagrelor or prasugrel)
stable patients undergoing elective PCI use clopidogrel
145
secondary prevention of ischemic stroke
monotherapy of aspirin or clopidogrel or aspirin/dipyridamole
146
parenteral anticoagulants
heparin (inhibits clotting factors)
low molecular weight heparin: enoxaparin/dalteparin (inhibit clotting factor X)
fondaparinux (inhibit clotting factor X)
argatroban, bivalirudin (both are direct thrombin inhibitors)
147
oral anticoagulants
warfarin (inhibits clotting factor synthesis)
DOACs: rivaroxaban, apixaban, edoxaban, dabigatran (all of these inhibit clotting factor X)
148
fibrinolytic drugs
alteplase, tenecteplase, reteplase
plasminogen activators
149
inhibitors of fibrinolysis
aminocaproic acid
tranexamic acid
150
how are anticoagulants usually used long term
start with parenteral then transition to oral
151
bleeding risks ranked
fibrinolytics > anticoagulants > antiplatelets
152
heparin
endogenously produced by mast cells
bind antithrombin and enhance its activity
inactivates thrombin and factor Xa, IXa, XIa, XIIa
high doses decrease platelet activation
can have resistance bc high concentration of heparin binding proteins or antithrombin 3 activity
used for treatment/prevention PE/DVT, acute coronary syndrome, prevent clotting in extracorporeal devices
adverse effects - thrombocytopenia, HIT, osteoporosis
monitor PTT REQUIRED
protamine sulfate antidote
153
low molecular weight heparins (enoxaparin, dalteparin)
accelerate antithrombin neutralization and selectively inhibits factor Xa
renal elimination
adverse effects - thrombocytopenia, sometimes HIT
no routine monitoring
protamine sulfate antidote
used for VTE treatment/prophylaxis, acute coronary syndrome
154
fondaparinux
accelerates antithrombin neutralization and has high specificity for factor Xa
renal elimination
adverse effects - bleeding
no routine monitoring
used for VTE treatment/prophylaxis, off label HIT treatment
155
heparin induced thrombocytopenia
IgG antibody directed against endogenous platelet factor 4, in complex with heparin activates platelets leading to thrombosis
thrombocytopenia bc macrophages remove IgG coated platelets
type 1 - mild drop of platelets that returns to normal
type 2 - clinically significant due to HIT antibodies
5-10 days after initiation of heparin
thrombosis is a risk
156
direct thrombin inhibitors (argatroban, bivalrudin)
for patients undergoing PCI for ACS (usually history of HIT)
reversibly binds active site of thrombin preventing coagulation
157
warfarin
inhibits vitamin K oxide reductase
reduces production of vitamin K dependent coagulation factors (II, VII, IX, X) AND protein C and S
bridging with parenteral anticoagulant required for at least 5 days until INR in therapeutic range
many drug drug and drug food interactions
REQUIRED monitoring of INR
used for VTE tx/prophylaxis, stroke prophylaxis and atrial fibrillation, reduce risk thromboembolism with mechanical heart valves
reversal by vitamin K and 4 factor PCC
158
direct oral anticoagulants
oral factor Xa inhibitors - apixaban, rivaroxaban, edoxaban
oral direct thrombin inhibitor - dabigatran
-fixed dosing, few interactions, less frequent monitoring
used to prevent thromboemolism in nonvalvular atrial fibrillation, VTE tx/prophylaxis
159
dabigatran
prodrug converted in vivo
parenteral anticoagulant required prior
dyspepsia is common
idarucizumab reversal agent
160
apixaban
metabolized by CYP3A4
dose adjustment for NVAF, no adjustment for VTE tx
161
rivaroxaban
renal dose adjustment for NVAF
metabolized by CYP3A4
andexanet alfa reversal
162
edoxaban
parenteral anticoagulant therapy required prior to initiation for VTE treatment
renal dose adjustment
163
fibrinolytic drugs
altepase - recombinant form of human tissue plasminogen acivator
reteplase - longer half life and less fibrin specific
tenecteplase - prolonged half life and greater binding affinity for fibrin
convert plasminogen to plasmin
main factor of effectiveness is time
used for acute ischemic stroke, STEMI, acute high risk PE
IV only
164
4 factor prothrombin complex concentrate
provide vitamin K dependent clotting factors (II, VII, IX, X) and protein C and S
used for hemorrhage from warfarin, factor Xa inhibitor, or direct thrombin inhibitor
165
fresh frozen plasma
contain all coagulation factors
used for trauma, liver disease, DIC
166
cryoprecipitate
insoluble coagulation factors (fibrinogen, factor III, XIII, vWF, fibronectin)
for disorders with specific clotting factors
167
fibrinogen concentrate
contains only fibrinogen
168
vitamin K
phytonadione
reversal of warfarin, newborn, vitamin K deficiency without liver disease
oral - more predictable
IV - for severe bleeding
169
von Willebrand disease treatment
desmopressin
von willebrand factor concentrate
tranexamic acid/epsilon aminocaproic acid to prevent fibrinolysis
cryoprecipitate
170
hemophilia A treatment
emicizumab
intavenous factor VIII
desmopressin for bleed
171
hemophilia B treatment
IV factor IX replacement
prothrombin complex concentrates
172
novoseven RT
reecombinant activated vactor VIIa
replaces deficient activated factor VII, may activate Xa and IXa
used for bleeding in hemophilia with inhibitors
173
steps of hemostasis
1. vascular constriction
2. platelet plug formation
3. formation of blood clot
4. fibrous tissue growth into blood cloth for permanent closure
174
vascular constriction
trauma to vessels result in vasoconstriction and reduced blood flow
myogenic contraction - immediate reflex, initial response to injury, smooth muscle contraction utilizes autocoid factors
autocoid factors - damaged endothelium activates platelets, platelets release serotonin, calcium, ATP, ADP, thromboxane A2 to stimulate constriction and platelet aggregation
175
platelet plug formation
platelets contact damaged surface (swell, irregular form), contractile proteins contract and release granules w activating factors, platelets stick to vWF and collagen, platelets secrete ADP and thromboxane A2 to attract more platelets
vascular damage exposes collagen which binds vWF and uncoild it so it can bind BP Ibalpha which adheres and activates platelets
176
formation of blood clot
fibrin of blood clot adheres to damaged surface
steps in coagulation - cascade of chemical reactions (prothrombin activator), conversion prothrombin to thrombin, conversion fibrinogen to fibrin to enmesh platelets/clot/plasma
retraction expresses serum from the clot
177
fibrous tissue growth
clot is invaded with fibroblasts
clot is dissolved by plasminogen (activated very slowly to plasmin by tissue plasminogen activator)
178
hemoglobin
tetrameric protein
cooperative binding of oxygen
several factors influence binding and dissociation
carries CO2 to the lungs
179
heme
ring with iron in center
one linked to each subunit of Hb
site of oxygen binding
synthesis in liver and erythrocyte producing cells in marrow (first and last 3 steps in mitochondria, intermediate in cytosol)
breakdown creates bilirubin which is conjugated in the liver or excreted as bile, conjugated goes to intestine and excreted in feces
180
iron
without oxygen it is pulled out of the plane of the heme ring
with oxygen it moves into the plane
181
oxygen binding
changes Hb from T to R state
disrupts salt bridge connection so alpha 1 beta 1 no longer bound to alpha 2 beta 2
binding 1 O2 makes binding others easier
182
oxidized hemoglobin
when iron is in ferric state (Fe3+)
oxygen carrying capacity is lost
183
oxygen dissociates with
decreased pH
2,3 BPG
binding CO2
increased temperature
184
carbon monoxide
competes wtih oxygen for binding
oxygen capacity reduced in direct proportion to CO-Hb concentration
185
carbonic anhydrase
converts CO2 to hydrogen and bicarbonate
reverses in lungs
186
nitric oxide
must accompany hemoglobin to enable blood vessels to dilate and supply oxygen
187
erythrocytosis (polycythemia)
too many RBCs causing elevated hematocrit and hemoglobin
primary or secondary
rule out false elevations due to decrease in plasma volume
asymptomatic at first, then CNS signs (lethargy, forgetful) and excess cardiac preload (distended neck veins/hepatic congestion)
188
anemia
decrease in RBCs
hemolytic anemia - RBCs destroyed (intrinsic like membrane abnormalities or extrinisc like mechanical heart valves)
189
erythropoietin
stimulates RBC production
sensors in kidney and liver detect even mild hypoxia and induce hypoxia inducible transcription factor tp upregulate erythropoietin
190
relative polycythemia
increase in red cell mass bc decrease in plasma volume
191
absolute polycythemia
increase in red cell mass
primary - due to mutation
secondary - bc elevated erythropoietin
192
polycythemia vera
neoplastic
myeloproliferative disorder - mutated activated tyrosine kinase leading to growth factor independence
EPO is low
can transform into acute myelogenous lymphoma
193
hemolytic anemia
increased RBC destruction
pale, weak, dyspnea, fatty changes, acute blood loss/shock
normocytic cells
increased EPO, accumulation bilirubin (jaundice), haptoglobin decreased, LDH increased, AST increased
intravascular - not with splenomegaly, due to mechanical fixation/complement activation/parasites/toxic factors
extravascular - less deformible RBCs removed by spleen (splenomegaly)
194
intrinsic hemolytic anemias
RBC membrane - hereditary spherocytosis, hereditary elliptocytosis
enzymes - G6OD deficiency, pyruvate kinase
globin synthesis - sickle cell, thalassemias
acquired membrane defect - parozysmal nocturnal hematuria
195
extrinsic hemolytic anemias
mechanical, antibodies, blood group incompatability, drugs/chemicals, hypersplenism
196
hereditary spherocytosis
defects in membrane skeleton that weaken links with membrane proteins
defective RBCs removed by spleen
RBCs - dark, lack central pallor
splenomegaly
cholelithiasis
present - often in childhood, splenomegaly, jaunduce
tx - splenectomy
197
G6PD deficiency
X linked
cells vulnerable to oxidative injury
exposure to environmental agent leads to oxidant production
heinz bodies - precipitated oxidized HgB that are removed by spleen macrophages causing bite cells
198
paroxysmal nocturnal hemoglobinuria
acquired abnormality in phosphatidylinositol glycan complementation group A gene (PIGA) for synthesis of cell surface proteins that anchor proteins to cell membrane
hematopoietic cells sensitive to complement lysis
sleep decreases pH which enhances complement fixation
can reduce hemolysis with monoclonal antibody again C5a
199
sickle cell
chronic hemolytic anemia with short RBC lifespan
microvascular obstruction and ischemia cause pain crisis
hemosiderosis and cholelithiasis can result
200
mechanical hemolytic anemia
shearing of RBCs
mechanical heart valves, clots in vessels, trauma
indirect hyperbilirubinemia, increased LDH/haptoglobin
201
antibody hemolytic anemia
warm - target Rh antigens, IgA opsonization of RBC followed by destruction, often autoimmune condition, associated with drugs
cold - autoantibodies target I antigen, IgM with opsonization affect distal parts of body, seen with infections
202
thalassemias
due to mutations in alpha or beta globin
degree of change depends on number of affected chains
tx - transfusions, iron chelation, splenectomy, luspatercept (beta thalassemia), hematopoietic stem cell transplant
203
beta thalassemias
2 genes (1 mutation is minor, 2 mutations is major)
cause inadequate formation of hemoglobin leading to microcytic red cells or apoptosis bc free alpha chains
standard anemia symptoms, abnormal facies, abdominal distention
204
alpha thalassemia
4 globin genes lying in tandem
remaining beta chains not as effective at delivering oxygen
1 deletion - no prob
2 deletions - minor change
3 deletions - HbH disease (4 beta chains, can precipitate in erythrocytes)
4 deletions - lethal w HbBarts (holds O2 too tightly), gamma 4 tetramers, hydrops fatalis
205
red blood cell properties
no mitochondria, no ATP from TCA cycle
use glycolysis to produce ATP
provide substrates for hexose monophosphate shunt and ropoport luebering shunt
206
hexose monophosphate shunt
produces 5 carbon sugars
returns carbons to glycolysis in RBCs
produces NADPH (reduces gluthione for antioxidant effect)
207
rapoport luebering shunt
increase synthesis 2,3 BPG
regulate affinity of hemoglobin for oxygen
208
cytochrome b5
reduces iron so it can transport oxygen
209
pyruvate converted to lactate
pyruvate is toxic (end product of glycolysis)
produces NAD for glycolysis
210
metabolic anemias
mutation in enzymes needed for RBC production
most common is G6PD deficiency (on X chromosome, lowers antioxidant protection, some malaria protection)
211
red cell membrane proteins
glycophorin has large negative charge (prevents aggregation)
band 3 is chloride bicarb exchanger
212
red cell cytoskeleton
membrane proteins associate with ankyrin and band 4.1
these associate with spectrin and actin
with other proteins cytoskeleton is formed
213
nutritional anemias
vitamin deficiencies (folate and B12 needed for nucleotide synthesis)
-slows mitosis of progenitors
-megaloblastic anemia
iron deficiency/lead poisoning
-decreased rate of heme synthesis
-microcytic hypochromic anemia
214
metabolic anemias
enzyme deficiencies
mainly glycolytic enzymes or hexose phosphate shunt
-pyruvate kinase deficiency
215
pyruvate kinase deficiency
last enzyme in glycolysis, produces half the ATP in the path
slows down path, PEP not removed, less NAD recycling
low ATP
water loss increases concentration of hemoglobin, cell becomes rigid
BUT blocked path increases 2,3 BPG which increases O2 delivering capacity
216
spheroytosis
CBC and blood smear indicative
diameter and volume decreased (microcytic)
reduced central pallor, increased Hb conc, hyperchromic
anemia and jaundcice bc loss and degradation of fragments
splenectomy can help reduce anemia
217
hemoglobin C
similar to sickle cell
affects beta globin chain
HbC less soluble, forms crystals
218
hereditary persistence of fetal hemoglobin
gene for F globin not switched off entirely
HbF present, higher oxygen affinity than HbA (adult form)
reduce symptoms and pathology
attempt to switch gene
219
iron deficiency anemia
mean cell volume (MCV) falls
hematocrit and hemaglobin fall
serum ferritin and iron levels fall
total iron binding capacity rises (decreased transferrin saturation)
RDW increased
-microcytic cells with increased pallor
220
anemia of chronic disease
inflammation increases cytokines and increased hepcidin which blocks ferroportin 1
decreased serum iron
normal to high ferritin
normal to low TIBC
normal RDW
inflammatory markers elevated
221
thalassemia labs
increased serum ferritin
normal to increased red blood cell distribution width
normal to increased serum iron
normal iron binding capacity
normal to increased transferrin saturation
222
B12 deficiency
megaloblastic with elevated MCV (similar to folate deficiency)
folate deficiency can lead to B12 deficiency
B12 absorbed in terminal ilium, bound to IF produced in stomach
folate absorbed in upper 1/3 of small intestine (celiac disease)
causes subacute combined degeneration of spinal cord, glossitis
223
aplastic anemia
supression of multipotent myeloid stem cell
bone marrow failure results in pancytopenia
224
myelophthisic anemia
anemia due to space occupying lesion in bone marrow
metastatic tumor or idiopathic fibrosis
-anemia often accompanied with thrombocytopenia and sometimes leukocytopenia
225
antigens
on surface of RBCs
inherited genes determine an individuals blood group by causing antigens (agglutinogens) on RBC surface
Hh is precursor for ABO blood groups
226
antibodies
in plasma
agglutinins - gamma globulins produced by bone marrow and lymph gland cells producing antibodies to antigens, IgM molecules
227
blood types
A - has A antigen, anti B antibody
B - has B antigen, anti A antibody
AB - has A and B antigens, no antibody
O - has no antigens, A and B antibodies
228
Rh factor
rhesus antigen D
presence of D protein = +
absence of D protein = -
(Rh negative person must first be massively exposed to elicit a response, like a first pregnancy)
so first pregnancy nothing happens but sencond pregnancy the antibodies are there and cause probs (similar to transfusion if person has already been exposed)
229
benefits of blood transfusion
replace blood lost during surgery or serious injury
restore oxygen carrying capacity
provide clotting factors to prevent or treat bleeding
230
risks of blood transfusions
transfusion transmitted disease
hemolytic reaction
bacterial infections
febrile reaction, transfusion associated circulatory overload, allergic reaction, TRALI, hep C, HIV, fatal hemolysis
231
if transfusion is incompatible what happens
agglutination (clumping) and hemolysis
232
acute hemolytic reactions to blood transfusion
hypotension, tachypnea, tachycardia, fever, chills, hemoglobinemia, hemoglobinuria, chest or flank pain (classic triad of fever, flank pain, red or brown urine)
secondary to preformed anti A or anti B antibodies
normocytic anemia develops
233
clinical response to acute transfusion reactions
stop transfusion immediately but leave IV attached, dont discard bag
supportive care, begin infusion of normal saline
from other arm obtain sample for direct antiglobulin test, plasma free hemoglobin level, and repeat type and cross match
alert blood bank
if DIC heparinization should be considered
234
delayed transfusion reaction
due to reexposure to foreign red cell antigen previously encountered (Rh)
3-30 days
hemolysis is extravascular and generally less severe
no tx needed
235
febrile reaction
sensitivity of clients blood to WBCs, platelets, or plasma proteins
cytokines and antibodies to leukocyte antigens reacting with leukocytes or leukocyte fragments
fever, chills, warm flushed skin
236
allergic reaction (urticarial)
sensitized to the antigens in the donor unit
IgE mediated with release of histamines by mast cells and basophils
hives, urticaria
237
allergic reaction (anaphylaxis)
rapid onset of anaphylaxis (shock, hypotension, angioedema, respiratory distress)
rapid recognition and concomitant action
signs - dyspnea or stridor, hypotension, tachycardia, cardiac arrythmia, cardiac arrest
238
transfusion related acute lung injury (TRALI)
antibodies in transfused blood activate recipients immune system causing hypoxia and massive pulmonary edema
usually donor plasma with high titer anti HLA class II antibodies that bind recipient leukocytes that release mediators and increase capillary permeability
239
sepsis
contaminated blod administered
signs - high fever, chills, vomiting, diarrhea, hypotension
240
circulatory oerload
blood administered faster than circulation can accomodate
signs - cough, dyspnea, hypertension, tachycardia
called TACO (transfusion associated circulatory overload)
241
leukocytosis
white blood cell count increased
normal response to infectious or inflammatory process
increased marrow production, increased release from marrow, decreased margination, decreased extravasation into tissues
morphology changes - dohle bodies, cytoplasmic/toxic vacuoles
242
leukemoid reaction
leukocytosis in excess with left shift caused by process other than leukemic conditions
-medications, asplenia, nonhematologic malignancy, C diff, TB, pertusis
extreme increase in granulocytes
243
leukoerythroblastosis
process that distorts the marrow vasculature and cause abnormal release of precursors into peripheral blood
244
leukopenia
decreased WBCs
most frequently seen with neutrophils but can also be leukopenic
from lymphocyte activation and cytokine/growth factor balance
245
neutrophilia
increased neutrophils
acute bacterial infections, sterile inflammation, chronic inflammation, drugs
bc increased marrow production or decreased activation of neutrophil adhesion molecules
246
dohle bodies
remnants of endoplasmic reticulum and are products of cytokine activity in induction and shortened activity of neutrophil activation
present in conditions with increased neutrophil lysosomal activity
247
neutropenia
reduction in neutrophils
drugs most common etiology
inadequate or ineffective granulopoiesis (suppress hematopoietic stem cells, ineffective hematopoiesis, inherited defects)
accelerated removal (immune mediated injury, splenomegaly, increased activation, hypercellular marrow)
-increased infections
-can treat with G-CSF
248
eosinophilia
increase in eosinophils
release of chemotactic factors from mast cells, no sequestering of eosinophils in lymph nodes
allergic reactions, parasitic infections, vasculitis, addisons disease, malignancy
often with accompanying necrosis
249
eosinopenia
decreased eosinophils
caused by hypercortisolism (cushings syndrome, corticosteroids), sequestering eosinophils in lymph nodes, acute bacterial infections
250
basophilia
increase in basophols
chronic myeloproliferative disorders, immediate hypersensitivity reactions, malignancy
251
basopenia
decreased basophils
may be difficult to distinguish from normal
252
mast cells
increased at sites of recurrent allergic reactions, with autoimmune conditions, osteoporosis, chronic renal or liver failure, with parasites, lymph nodes draining cancers
disorders - urticaria pigmentosum, solitary mastocytoma, systemic mastocytosis, pruritis and swelling of tissues
possible decrease of numbers wtih steroids
253
systemic mastocytosis
clonal expansion of mast cells
usually only noted in peripheral distribution sites and bone marrow
causes pruritis, flushing, palpitations, vascular collapse, gastric distress, lower abdominal pain, recurrent headaches
tx - antihistamine/proton pump inhibitors, glucocorticoids, epinephrine
254
monocytosis
increase in monocytes
chronic inflammation or malignancy, infections, immunological diseases, neutropenic conditions
255
monocytopenia
similar to neutropenia
acute infections, stress, glucocorticoids, neoplasia, myelotoxic drugs
256
lymphocytosis
increase in lymphocytes
infection, drugs, graves disease
caused by increased production or decreased entry into lymph nodes
can be atypical
257
lymphocytopenia
decrease in lymphocytes
caused by viruses, immunodeficiency, autoimmune conditions, corticosteroid use, radiation
because of decreased production or increased destruction
258
lymphadenopathy (acute lymphadenitis)
antigenic stimulation including infections causing B and T cell hyperplasia
-phagocytosis of bacteria and necrotic cells, abcess possible with bacterial infections, draining sinuses can occur
259
lymphadenopathy (chronic lymphadenitis)
chronic antigen stimulation - follicular hyperplasia with humoral immune response (RA, early HIV, toxoplasmosis), paracortical hyperplasia with cell mediated responses (viral infections), mixed B and T cell hyperplasia, sinus histiocytosis (increased number and size of cells that line lymphatic sinusoid)
260
oral iron
ferrous sulfate
ferrous gluconate
ferrous fumarate
261
parenteral iron
iron dextran
iron sucrose
ferric gluconate
ferric coarboxymaltose
ferumoxytol
262
others used in anemia
cyanocobalamin
hydroxycobalamin
folic acid
leuvocorin
263
iron antidote
deferozamine
264
hematopoietic growth factors
erythropoietin (epoietin)
darbepoetin
filgastim (G-CSF)
pegfilgrastin
sargramostim (GM-CSF)
interleukin 11
oprelvekin
265
thrombopoietin agonists
romiplostim
eltrombotag
266
adaptation to iron defeciency
suppression of hepcidin and tissue hypoxia
erythropoietin increases bc increased hypoxia inducedible factor 2 alpha (HIF 2 alpha)
erythropoiesis increasedand hypochromic microcytic red cells produced
increased erythropoiesis decreases hepcidin
HIF 2 alpha increases duodenal divalent metal transporter 1 to increase the transfer dietary iron from the lumen to enterocytes
267
oral vs IV iron
treat uncomplicated patients with oral iron
conditions for IV iron - pregnancy, IBD, gastric surgery, CKD, ongoing blood loss
268
iron is absorbed where
duodenum and proximal jejunum
iron in heme is readily absorbed, free iron must be reduced to ferrous iron before being absorbed
269
how is iron transported in the plasma
bound to transferrin
it enters maturing erythroid cells by receptor mediated endocytosis
iron stored as ferritin
270
adverse effects of administered iron
oral - nausea, epigastric discomfort, diarrhea/constipation, black stools
parenteral - nausea/vomiting, fever, arthralgias, back pain, bronchospasm, anaphylaxis
271
acute iron toxicity
necrotizing gastroenteritis followed by shock, metabolic acidosis, coma, death
272
chronic iron toxicity
hemachromatosis
organ failure and death
273
contraindications
anemia not caused by iron deficiency
state of iron overload
parkinsons disease
274
therapeutic uses
prevention and treatment of iron deficiency anemia
oral - continue 3-6 months after correction
parenteral - less allergenic, may provide entire dose needed
275
ferrous iron
most efficiently absorbed
used OTC
contraindications - primary hemachromatosis, peptic ulcer disease, ulcerative collitis
276
iron dextran
must give test dose before, must give using Z track method
adverse effects - anaphylaxis, death, nausea, urticaria
277
ferric gluconate
primarily in dialysis patients
less hypersensitivity but administer slowly and observe
278
iron sucrose
less hypersensitivity but administer slowly and observe
dialysis patients, non dialysis CKD, IBD, chemo induced anemia, peripartum period, gastric bypass, heavy uterine bleeding
279
ferumoxytol
give slowly bc infusion reaction hypotension
cause brighter signal on MRI
280
ferric carboxymaltose
tighter binding of elemental iron to carbohydrate polymer
281
folic acid
cofactor for synthesis of amino acids, purines, DNA
ensure no underlying B12 deficiency
treat megaloblastic anemia from folic acid deficiency (inadequate intake, impaired absorption)
given in pregnancy
282
leucovorin
folic acid plus rescue cells exposed to folate antagonists
used for prophylaxis of methotrexate toxicity and during fluoruracil therapy
283
vitamin B12
cyanocobalamin and hydrocobalamin
treat megaloblastic anemia caused by B12 deficiency
284
erythropoietin
used for anemia of chronic renal failure, pure RBC aplaia, secondary anemias
can cause hypertension and thrombotic complications
285
filgrastim
granulocyte CSF
increases neutrophils and hematopoietic stem cells
286
sagramostim
granulocyte macrophage CSF
increase neutrophils, megakaryocytes, erythroid cells, T cells
287
myeloid growth factor adverse effects
throbbing bone pain, leukocytosis, hyperuricemia
288
myeloid growth factor contraindications
chemo induced neutropenia, other severe neutropenia, peripheral blood cell mobilization, aplastic anemia
289
interleukin 11 (oprelvekin)
increase megakaryocytes, neutrophils, platelets, myeloid and lymphoid cells
causes fluid retention and edema
290
romiplostim/eltrombopag
increase platelet count
cause mild headache and marrow fibrosis/hepatotoxicity and hemorrhage
291
aplastic anemia
erythropoiesis and other cell lines affected bc suppression of myeloid stem cell (pancytopenia)
caused by - damage to stem cells, t cell suppression of stem cells, stem cell abnormalities
hypocellular, abundant fat, hemosiderin, hemorrhage and infections can happen
causes - anemia, thrombocytopenia, granulocytopenia, weakness, pallor
no splenomegaly, reduced reticuloytes
292
fanconi anemia
autosomal recessive
defect in complex for DNA repair
increased chromosomal breaks
early marrow hypofunction, congenital anomalies, bone anomalies
can treat with blood and marrow stem cell transplant
293
pure red cell aplasia
primary marrow disorders that only affect erythroid precursors
associated with neoplasms, drug exposures, autoimmune disorders, parvo
tx - thymoma removal, plasmapheresis, treat underlying conditions
294
splenomegaly
bc infection, vascular congestion/portal hypertension, lymphohematogenous disorders, immune inflammatory conditions, storage diseases
295
splenic infarct
secondary to occlusion of major splenic artery or branches including emboli
sickle cell anemia with autosplenectomy due to vascular occlusion
296
thymic hypoplasia/aplasia
digeorge syndrome with several deficits in cell mediated immunity and abnormalities of thyroid
297
thymus hyperplasia
enlarged with presence of lymph follicles
seen in myasthenia gravis and autoimmune disorders
298
thymoma
tumor of thymic epithelium
cough, dyspnea, superior vena cava syndrome, myasthenia gravis, hypogammaglobinemias, SLE, pure red cell aplasia
299
stroma of lymph tissue
composed of reticular fibers and reticular cells
300
cells of lymph tissues
lymphocytes - immune effector cells and precursor to plasma cells
macrophages - phagocytosis and antigen processing
reticular cells - structural support
plasma cells - antibody production
301
loose lymph infiltration
collections of lymphocytes infiltrating into tissues where inflammation exists
302
lymph nodules
collections of lymphoid cells found as scattered lymph tissue infiltrations and in lymph organs
primary - dont contain germinal centers (mature B cells are proliferating during immune response)
secondary - contains germinal centers
303
lymph nodule structure
germinal centers stain light bc active lymphocytes, macrophages, plasma
cortex stains basophilic bc the large number of small lymphocytes
304
mucosa associated lymphoid tissues
in mucosa of digestive, respiratory, genitourinary tracts
contain lymphocytes,
IgA, APCs, lymph nodules
lack afferent lymph vessels (dont filter)
305
tonsils
structure - not totally encapsulated, trabeculae and reticular connective tissue support, epithelial crypts, no afferent lymphatics, lymph nodules
-palatine and lingual covered by stratified squamous nonkeratinized epithelium
-pharyngeal covered by pseudostratified ciliated columnar epithelium
function - expose lymphocytes to antigens, immunological responses
306
peyers patches
lymph nodules crowded together under GI structures
no afferent vessels
M (microfold) cells with short apical folds, basal surface forms intracellular pocket with lymphocytes and dendritic cells
antigens in gut bound by M cells and undergo transcytosis for antigen presentation, IgA transported to gut to bind antigen
307
lymph node structure
capsule on outside with trabeculae that extend deep into node
sinuses deep to capsule along trabelulae
trabeculae and sinuses convey lymph from afferent vessels into node
vessels course in and out between trabeculae to bring blood in and out
hilum - where arterioles enter and veins leave
cortex - primary and secondary lymph nodules (mainly B lymphocytes)
paracortex - where lymph enters node via high endothelial venules (mainly T lymphocytes)
medulla - sinuses and cords of lymph tissue, sinuses continuous with cortical sinuses and converge to form efferent vessels
308
medullary sinuses
contain macrophages and sometimes neutrophils if draining an infected area
-contains reticular cells with long processes and elongated nuclei (final filter for lymph)
309
medullary cords
contain b and t cells, extend from paracortex
310
HEVs
endothelial lining of cuboid cells with apical surface glycoproteins and integrins to facilitate rapid diapedesis
311
spleen functions
facilitate immune response to blood borne antigens (white pulp)
filter defective blood and platelets (red pulp)
312
spleen structure
-soft tissue enclosed by capsule covered with simple squamous mesothelium
-extending in hilum and capsule are trabeculae that convey blood vessels
-pulp supported by reticular fibers but not organized
313
red pulp
splenic cords
contains reticular cells, macrophages, lymphocytes, plasma cells, RBCs, platelets, granulocytes
314
spleen blood circulation
splenic artery divides as it penetrates hilum
branches course trabeculae
trabecular artery leaves trabecula enveloped by lymphocytes (mainly T) and name changes to central artery with periarterial lymphatic sheath
central artery leaves white pulp called pulp artery
then divide into penicilliary arterioles before becoming capillaries
315
open circulation and red pulp
-capillaries open into parenchyma of red pulp between splenic cord (blood can leave and reenter sinusoid)
-sinusoids contain large irregular lumens with elongated endothelial cells with intercellular clefts forming leaky barrel w hoops of reticular fibers
-inflexible RBCs cant pass througgh and removed by macrophages
316
white pulp
lymph tissue arranged in periarterial lymph sheaths (PALS)
lymph cells surrounding the central arteries are mainly T cells
lymph nodules adjacent to central artery and PALS
317
marginal zone
at periphery of lymph nodules the reticular fibers and cells form concentric layers and delimited lymph tissue from red pulp
receives T and B cells
initiate immune responses
318
thymus structure
complete capsule
two lobes, thousands of lobules
reticular cell support by epithelial cells that arent phagocytic
no lymph nodules (no B cells)
cortex wtih small lymphocytes (high mitotic rate, high death rate)
medulla with medium and large lymphocytes, epithelial reticular cells, hassalls corpuscles
319
thymus function
lymphocyte production
manage lymphocytes for immune system
forms thymic hormones
doesnt filter blood or lymph
not involved in antibody formation
NO lymph nodules
320
thymus cell types
thymocytes
epithelial reticular cells
macrophages
321
epithelial reticular cells
-form meshwork called cytoreticulum, branches attach by desmosomes
-interstices packed with lymphocytes
-desmosomes and tonofilaments indicate epithelial character
-the reticular cells are secretory and possess granules with thymic growth factors for development of t cells
-form thymic (hassall) corpuscles in medulla
322
thymus vasculature
branches of subclavian arteries function as thymic arteries and enter capsule at many places
enter medulla and form arterioles (require sheath of epithelial cells)
capillaries in thymus cortex are nonfenestrated continuous with thick basal lamina creating blood thymus barrier (prevent exposing t cells to antigens while developing)
323
where do t cells proliferate and differentiate
thymus cortex
324
thymus selection
positive - in cortex, select t cells with functional TCRs
negative - in medulla, select t cells that do not tightly bind self antigens
after selection the t cells enter the medulla and leave by efferent lymphatics
